{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:50:22Z","timestamp":1782280222821,"version":"3.54.5"},"posted":{"date-parts":[[2025,1,2]]},"group-title":"Molecular Biology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  The glycoprotein hormones of humans, produced in the pituitary and acting through receptors in the gonads to support reproduction and in the thyroid gland for metabolism, have co-evolved from invertebrate counterparts\n                  <jats:sup>1,2<\/jats:sup>\n                  . These hormones are heterodimeric cystine-knot proteins; and their receptors bind the cognate hormone at an extracellular domain and transmit the signal of this binding through a transmembrane domain that interacts with a heterotrimeric G protein. Structures determined for the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric\n                  <jats:sup>3\u20136<\/jats:sup>\n                  despite compelling evidence for their functioning as dimers\n                  <jats:sup>7\u201310<\/jats:sup>\n                  . Here we describe the cryo-EM structure of the homologous receptor from a neuroendocrine pathway that promotes growth in a nematode\n                  <jats:sup>11<\/jats:sup>\n                  . This structure is an asymmetric dimer that can be activated by the hormone from that worm\n                  <jats:sup>12<\/jats:sup>\n                  , and it shares features especially like those of the thyroid stimulating hormone receptor (TSHR). When studied in the context of the human homologs, this dimer provides a structural explanation for the transactivation evident from functional complementation of binding-deficient and signaling-deficient receptors\n                  <jats:sup>7<\/jats:sup>\n                  , for the negative cooperativity in hormone action that is manifest in the 1:2 asymmetry of primary TSH:TSHR complexes\n                  <jats:sup>8,9<\/jats:sup>\n                  , and for switches in G-protein usage that occur as 2:2 complexes form\n                  <jats:sup>9,10<\/jats:sup>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2024.12.31.630923","type":"posted-content","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T11:50:17Z","timestamp":1735818617000},"source":"Crossref","is-referenced-by-count":1,"title":["Structure of an LGR dimer \u2013 an evolutionary predecessor of glycoprotein hormone receptors"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0760-1493","authenticated-orcid":false,"given":"Zhen","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuobing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kloss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver B.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing 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